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Army Research Drives Brain Injury Science

By Cheryl PellerinAmerican Forces Press Service

WASHINGTON, April 18, 2012  With $633 million and 472 active research projects on traumatic brain injury alone, the Army is driving the science behind this neglected public health problem that affects everyone from kids on the sports field to service members in Afghanistan.

TBI, and especially mild TBI, “is essentially a frontier of medicine,” Army Col. (Dr.) Dallas Hack, director of the Army’s Combat Casualty Care Research Program, said in a recent interview with American Forces Press Service.

From 2000 to 2011, just over 133,000 soldiers were diagnosed with TBI. For the Defense Department as a whole in that period, 220,000 service members were diagnosed, according to an Army behavioral health specialist.

Traumatic brain injuries range from severe to moderate to mild and can be caused by a bump, blow or jolt to the head or a penetrating head injury that disrupts normal brain function.

On the battlefield, Hack said, fewer than 25 percent of brain injuries are combat related. Most are caused by training injuries, vehicle accidents and a range of other activities.

Severe brain injuries are easy to diagnose, Hack said. Any kind of a computed tomography, or CT, scan can show the resulting physical defect.

CT scans combine a series of X-ray views taken from many different angles with computer processing to produce cross-sectional images of soft tissues inside the brain.

It’s a little more difficult to diagnose moderate TBI, he said, “although some of the more advanced imaging, even [magnetic resonance imaging, or MRI] scans generally do a decent job.”

MRI machines use powerful magnets and radio waves to create pictures of the internal brain.

“Where it is so difficult and where we as a culture and as a profession basically ignored it for all these years,” Hack said, “is in the mild TBI area.”

To improve the spectrum of diagnosis-to-treatment of mild TBI, he said, the research program pushes the science with partners like university researchers, and even organizations like the National Football League and the National Hockey League, sports whose players are at risk for concussion, also called mild TBI.

Research being funded includes a range of neuroimaging or brain scanning technologies; quantitative electroencephalography or brain mapping, blood tests for biomarkers of brain injury, and even drugs that may prevent injuries from mild brain trauma.

Brain imaging is “probably the current best we can do,” Hack said, but scientists often don’t have enough data to interpret mTBI scans.

“The fact is,” he added, “that on the milder injuries you don’t see physical defects but you can see functional issues.”

Studies are ongoing with functional MRIs, which rather than showing brain structures show brain activity by tracking the uptake of glucose, the brain’s source of energy.

Other imaging research targets a new kind of CT scan called single-photon emission computed tomography, or SPECT, which shows how blood flows through arteries and veins in the brain.

A technique called DTI, for diffusion tensor imaging, is a special version of MRI that measures the direction of water molecules in the brain, Hack said, so scientists can follow the physical path of nerve tracts in the brain.

Brain mapping, called quantitative EEG, can automatically detect and locate abnormal brain activity, he added, “or what we call silent seizures. We often see these soon after an injury and we have studies that are working on getting [Food and Drug Administration] approval” to use the technique in mTBI.

The program’s biomarker studies are producing devices that can test the blood for proteins unique to brain cells and indicate whether brain cells are damaged.

“When brain cells die and break [apart],” Hack said, “they spill their contents into the brain fluid. Some of that gets across into the blood and we can measure it.”

An application for FDA approval of the device will be submitted sometime in 2013, the physician said, “and hopefully we can have an approved test by the end of 2013.”

Eye movements are another way to get a look inside the brain.

“Certain kinds of eye movements are affected by even mild brain injury,” Hack said, “so we have some projects in that. We have others in sensory function. Balance, for instance, or vestibular function, is also quite sensitive to brain injury.

In such fledgling brain science studies, the researchers have to make sure they’re diagnosing the right conditions.

“Confounders are other conditions that could cause the same problems,” Hack said, “and we need to make sure in our studies that we’re able to differentiate brain injury from other conditions that can cause functional impact,” including Alzheimer’s disease, for example, or even lack of sleep or poor nutrition.

The program’s three-pronged approach to understanding mTBI, he said, is to determine whether there is brain cell damage, where the damage is and its functional impact.

“The science behind all of that is still very rudimentary, so we’re spending a lot of effort in those areas,” he said.

The program also funds drug trials, some of which examine existing drugs to see if they have a beneficial effect on brain inflammation, which can occur after a brain injury.

Atorvastatin, whose brand name is Lipitor, “is one of the drugs that has shown a benefit [on inflammation] in brain cells.”

The program is working with the National Institutes of Health on a phase III clinical trial of the female hormone progesterone.

“Progesterone is essentially a steroid that also is a female hormone but it is called a neurosteroid as well,” Hack said. “It has a positive benefit on brain inflammation.”

He added, “We don’t think there’s any one drug that will [help those with mTBI]. This is a complex problem and it’s going to take multiple approaches to solving it.”